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Sirtuin1, not NAMPT, possesses anti-inflammatory effects in epicardial, pericardial and subcutaneous adipose tissue in patients with CHD

J Transl Med. 2023 Sep 21;21(1):644. doi: 10.1186/s12967-023-04518-4.

ABSTRACT

BACKGROUND: Inflammation in cardiac adipose tissue (AT) is associated with atherosclerosis. We investigated whether the epicardial-, pericardial and pre-sternal subcutaneous AT (EAT, PAT and SAT) expression of Sirtuin1 (SIRT1) and nicotinamide phosphoribosyl transferase (NAMPT) are involved in the inflammatory process in coronary heart disease (CHD), and potentially associated to nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related markers, macrophage polarization markers, cell markers and the cardiometabolic profile.

METHODS: In this cohort study performed between 2016 and 2018, EAT, PAT and SAT biopsies were retrieved from 52 CHD patients (77% men, median age 67) undergoing open-chest coronary artery bypass grafting (CABG), and 22 patients (50% men, median age 69) undergoing aortic valve replacement serving as controls. AT samples were snap-frozen at – 80 °C until RNA extraction and AT expression of actual markers, relatively quantified by PCR. Circulating SIRT1 and NAMPT were measured with Enzyme-linked immunosorbent assays (ELISAs). Non-parametric statistical tests were mainly used, including Friedman’s test coupled to Wilcoxon signed-rank test and Spearman Correlation.

RESULTS: SIRT1 and NAMPT levels were similar in CHD and controls. In CHD, SIRT1 and NAMPT were inter-correlated in all AT compartments (r = 0.37-0.56, p < 0.01, all), and differently expressed between compartments, with the highest expression in SAT, significantly different from EAT (p < 0.01, both). Circulating SIRT1 and NAMPT levels were inversely associated (r = – 0.32, p = 0.024). In EAT and SAT, SIRT1 expression was inversely associated with IL-18 (r = – 0.43 and r = – 0.38, p < 0.01, both), whereas NAMPT expression was positively associated with the NLRP3 inflammasome-related markers in all compartments (r = 0.37-0.55, p < 0.01, all). While SIRT1 and NAMPT correlated to nitric oxide synthase 2 (NOS2), especially in SAT (r = 0.50-0.52, p ≤ 0.01, both), SIRT1 expression was related to endothelial cells, and NAMPT to macrophages. SIRT1 levels were correlated to weight and waist (r = 0.32 and r = 0.38, p < 0.03, both) and inversely to triglycerides and glycated haemoglobin (HbA1c) (r = – 0.33– 0.37, p < 0.03, all), the latter positively correlated to NAMPT concentration (r = 0.39, p = 0.010).

CONCLUSION: The study indicates that targeting SIRT1, with its anti-inflammatory properties, may be a novel anti-inflammatory strategy in preventing atherosclerosis and CHD progression. NAMPT may be an early player in AT inflammation, mediating/reflecting a pro-inflammatory state.

TRIAL REGISTRATION: Registration: Clinicaltrials.gov ID: NCT02760914, registered the 5th of February 2016, http://clinicaltrials.gov/NCT02760914.

PMID:37730614 | DOI:10.1186/s12967-023-04518-4

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Correlation of the tumor escape phenotype with loss of PRELP expression in melanoma

J Transl Med. 2023 Sep 20;21(1):643. doi: 10.1186/s12967-023-04476-x.

ABSTRACT

BACKGROUND: Despite immunotherapies having revolutionized the treatment of advanced cutaneous melanoma, effective and durable responses were only reported in a few patients. A better understanding of the interaction of melanoma cells with the microenvironment, including extracellular matrix (ECM) components, might provide novel therapeutic options. Although the ECM has been linked to several hallmarks of cancer, little information is available regarding the expression and function of the ECM protein purine-arginine-rich and leucine-rich protein (PRELP) in cancer, including melanoma.

METHODS: The structural integrity, expression and function of PRELP, its correlation with the expression of immune modulatory molecules, immune cell infiltration and clinical parameters were determined using standard methods and/or bioinformatics.

RESULTS: Bioinformatics analysis revealed a heterogeneous, but statistically significant reduced PRELP expression in available datasets of skin cutaneous melanoma when compared to adjacent normal tissues, which was associated with reduced patients’ survival, low expression levels of components of the MHC class I antigen processing machinery (APM) and interferon (IFN)-γ signal transduction pathway, but increased expression of the transforming growth factor (TGF)-β isoform 1 (TFGB1) and TGF-β receptor 1 (TGFBR1). In addition, a high frequency of intra-tumoral T cells directly correlated with the expression of MHC class I and PRELP as well as the T cell attractant CCL5 in melanoma lesions. Marginal to low PRELP expression levels were found in the 47/49 human melanoma cell lines analysis. Transfection of PRELP into melanoma cell lines restored MHC class I surface expression due to transcriptional upregulation of major MHC class I APM and IFN-γ pathway components. In addition, PRELP overexpression is accompanied by high CCL5 secretion levels in cell supernatant, an impaired TGF-β signaling as well as a reduced cell proliferation, migration and invasion of melanoma cells.

CONCLUSIONS: Our findings suggest that PRELP induces the expression of MHC class I and CCL5 in melanoma, which might be involved in an enhanced T cell recruitment and immunogenicity associated with an improved patients’ outcome. Therefore, PRELP might serve as a marker for predicting disease progression and its recovery could revert the tumorigenic phenotype, which represents a novel therapeutic option for melanoma.

PMID:37730606 | DOI:10.1186/s12967-023-04476-x

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Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration

BMC Public Health. 2023 Sep 20;23(1):1830. doi: 10.1186/s12889-023-16523-9.

ABSTRACT

BACKGROUND: The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.

METHODS: The overall objectives of our ‘Coronavirus: Mental Health and the Pandemic’ study were to explore UK adults’ experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of ‘Inequalities and mental health during the Coronavirus pandemic in the UK’ and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.

RESULTS: Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.

CONCLUSIONS: The pandemic is taking a long-term toll on the nations’ mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.

PMID:37730605 | DOI:10.1186/s12889-023-16523-9

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Web-based standardized patient simulation for taking anamnesis: an approach in nursing education during the pandemic

BMC Nurs. 2023 Sep 20;22(1):325. doi: 10.1186/s12912-023-01486-4.

ABSTRACT

BACKGROUND: To address the challenges in nursing education brought about by the pandemic, this study aimed to evaluate the use of a web-based standardized patient practice in the development of nursing students’ anamnesis taking skills and their views about its application.

METHOD: We conducted a descriptive intervention study with 39 s-year nursing students. The students completed anamnesis using the standardized patient practice in line with a scenario with real standardized patients in a web-based environment with audio and video.

RESULTS: The total scores of students’ anamnesis skills were low. The agreement between the total scores, scores obtained from the health patterns, and each item in the control list was statistically significant (p < 0.05).

CONCLUSION: Web-based standardized patient practice is an alternative for clinical practice facilitating the gaining of competencies in making holistic nursing diagnoses under conditions that limit face-to-face interactions, such as pandemics.

PMID:37730596 | DOI:10.1186/s12912-023-01486-4

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The impact of journal clubs on postgraduate medical education in China

BMC Med Educ. 2023 Sep 20;23(1):683. doi: 10.1186/s12909-023-04669-4.

ABSTRACT

PURPOSE: Journal clubs hold significant importance in medical education, with numerous studies highlighting their contributions worldwide. However, studies specifically examining their role in China, particularly among Chinese medical postgraduates categorized into academic and clinical types, remain scarce. This research aims to investigate the participation, performance, and benefits of journal clubs, and explore the influence of student type and study phase on these aspects.

METHOD: A survey encompassing demographic information, participation rates, performance evaluations, and perceived improvements was distributed to postgraduates at Tongji Medical College of Huazhong University of Science and Technology. A total of 232 completed questionnaires were included for further analysis. Statistical analysis employed the Mann-Whitney U test and Gamma tests, with statistical significance set at p-value < 0.05.

RESULTS: Overall participation and performance in journal clubs among Chinese medical postgraduates were comparable to global findings. Notably, academic postgraduates exhibited higher levels of attendance rate and gained more research assistance than clinical postgraduates, while their performance levels were similar. When considering the study phase, a downward trend in academic postgraduates’ attendance rate and listening attitude and an upward trend in clinical postgraduates’ participation were observed with the seniority phase. Additionally, presentation comments, post-presentation progress, and research assistance showed improvements over time for both student types.

CONCLUSIONS: This study reveals academic postgraduates’ fatigue, contrasting with clinical postgraduates’ enthusiasm, and underscores academic postgraduates’ superior research assistance. To address these findings, we recommend supporting and encouraging scientific research training for clinical postgraduates, aiding academic postgraduates in better time management and reducing non-essential responsibilities, and implementing critical appraisal skill education.

PMID:37730595 | DOI:10.1186/s12909-023-04669-4

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Preliminary in vitro cytotoxic evaluation of Uncaria gambier (Hunt) Roxb extract as a potential herbal-based pulpotomy medicament

BMC Complement Med Ther. 2023 Sep 20;23(1):331. doi: 10.1186/s12906-023-04163-w.

ABSTRACT

BACKGROUND: The downfall of formocresol as a pulpotomy medicament highlights the importance of cytotoxic evaluation and the establishment of a safe concentration of dental material prior to its usage in the oral cavity. Uncaria gambir is an herbal plant that possesses antimicrobial, anti-inflammatory and antioxidant properties, suggesting its potential as an alternative medicament for pulpotomy. However, there are not many studies published on its cytotoxicity, with some using non-standardised techniques and reported variable outcomes. Here, we investigated the concentration and time-dependent toxicity of Uncaria gambir extract towards the M3CT3-E1 cell line and compared it with the gold standard pulpotomy medicament: mineral trioxide aggregate (MTA).

METHODS: Uncaria gambir extracts at concentrations ranging from 1000 to 7.8 µg/ml and MTA eluates at 4- and 48 h setting times were prepared. 10% dimethyl sulfoxide (DMSO) and culture media were used as positive and negative controls respectively. Cell viability on days 1, 2, 3 and 7 was analysed using Alamar Blue and Live and Dead Cell assay. Any morphological cellular changes were evaluated using transmission electron microscopes (TEM). Data were analysed using a two-way mixed Analysis of Variance (ANOVA).

RESULTS: The interaction between the concentration and exposure time on the fluorescence intensity of Uncaria gambir extract and MTA 48 h was found to be statistically significant (p < 0.001). No cytotoxic effects on the cells were exerted by both MTA 48 h and Uncaria gambir extract at a concentration below 500 µg/mL. TEM analysis and Live and Dead Cell assay for both materials were comparable to the negative control. No significant differences in fluorescent intensity were observed between Uncaria gambir extract at 500 µg/mL and MTA 48 h (p > 0.05).

CONCLUSION: Uncaria gambir extracts at a maximum concentration of 500 μg/mL are non-cytotoxic over time and are comparable to the MTA.

PMID:37730579 | DOI:10.1186/s12906-023-04163-w

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Corrected analysis of “the effects of bright light treatment on affective symptoms in people with dementia: a 24-week cluster randomized controlled trial” that accounts for clustering and nesting verifies conclusions

BMC Psychiatry. 2023 Sep 20;23(1):683. doi: 10.1186/s12888-023-05180-2.

ABSTRACT

In this correspondence, we explain the reasoning for invalidity of the analysis choices by Kolberg et al., and provide the results produced using correct statistical procedures for their study design. Reassuringly, we could verify the original conclusions. That is, results of the corrected statistical models are similar to the results of the original analysis. Regardless of the magnitude of difference that corrected statistical methods make, results and conclusions that are derived from invalid methods are unsubstantiated. By verifying the results, we allow the readers to be assured that the published conclusions in the study by Kolberg et al. now rest on a sound evidential basis.

PMID:37730572 | DOI:10.1186/s12888-023-05180-2

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Extended postpartum intimate partner violence and its associated factors: community-based cross-sectional study design

BMC Womens Health. 2023 Sep 20;23(1):501. doi: 10.1186/s12905-023-02649-w.

ABSTRACT

BACKGROUND: Intimate partner violence is a global problem that threatens mothers. It has multidimensional consequences but has not gained attention from scholars after childbirth.

OBJECTIVE: To assess the prevalence of extended postpartum intimate partner violence and its associated factors.

METHOD: A community-based cross-sectional study design was employed among 570 postpartum mothers in Arba Minch Town, Southern Ethiopia, from May 21st to June 21st, 2022. A pretested, face-to-face interviewer-administered structured questionnaire was used. Bivariable and multivariable logistic regression analyses were used. The level of statistical significance was declared at P < 0.05 with a 95% CI.

RESULTS: Overall, the prevalence of extended postpartum intimate partner violence was 45% (95% CI: 40.89, 49.20). Participants whose husband has no formal education (AOR = 3.62; 95%CI: 1.32, 9.90) and only secondary education (AOR = 2.96; 95%CI: 1.56, 5.48), husband alcohol consumption (AOR = 1.73; 95%CI: 1.06, 2.80), husband dominance in decision-making (AOR = 1.94; 95%CI: 1.13, 3.33), husband disappointment in the gender of the baby (AOR = 2.13; 95%CI: 1.28, 3.56), previous history of intimate partner violence (AOR = 5.71; 95%CI: 3.59, 9.07), and low social support (AOR = 4.37; 95%CI: 2.53, 7.55) were significantly associated factors.

CONCLUSIONS AND RECOMMENDATIONS: The prevalence of extended postpartum intimate partner violence was found to be high. Thus, increasing awareness of husbands with no formal education and having lower academic achievement, incorporating maternal social support assessment into maternity and child health care; teaching on alcohol reduction behavior and gender roles; and screening of mothers during the prenatal period should be given.

PMID:37730570 | DOI:10.1186/s12905-023-02649-w

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Impact of foliar fungicide application on the culturable fungal endophyte community of soybean seed in the Midwest U.S

Plant Dis. 2023 Sep 20. doi: 10.1094/PDIS-06-23-1122-RE. Online ahead of print.

ABSTRACT

The purpose of our study was to determine whether the application of quinone outside inhibitor (QoI) and pyrazole-carboxamide fungicides as a tank mix would impact the endophyte community of soybean seed. Field trials during 2018 in Iowa, South Dakota, and Wisconsin, USA, investigated the impact of a single combination fungicide spray at early pod set in soybeans. The composition of culturable endophytic fungi in mature soybean seed was assessed on three cultivars per state, with maturity groups (MG) ranging from 1.1 to 4.7. An unusually wet 2018 season delayed harvest, leading to a high level of fungal growth in grain. The survey included 1,080 asymptomatic seeds that were disinfested and individually placed on 5-cm-diameter Petri plates of acidified water agar. The survey yielded 721 fungal isolates belonging to 24 putative species in seven genera; taxa were grouped into genera based on a combination of morphological and molecular evidence. The dominant genera encountered in the survey were Alternaria, Diaporthe, and Fusarium. The study showed that the fungicide treatment reduced the incidence of Fusarium in Wisconsin seed, increased the incidence of Diaporthe in seed from all states, and had no impact on the incidence of Alternaria. This is one of the first attempts to characterize the diversity of seed endophytes in soybean, and the first to characterize the impacts of fungicide spraying on these endophyte communities across three states. Our study provides evidence that the impact of a fungicide spray on soybean seed endophyte communities may be influenced by site, weather, and cultivar maturity group. .

PMID:37729650 | DOI:10.1094/PDIS-06-23-1122-RE

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Reduced Postdischarge Incidents After Implementation of a Hospital-to-Home Transition Intervention for Children With Medical Complexity

J Patient Saf. 2023 Oct 1;19(7):493-500. doi: 10.1097/PTS.0000000000001155. Epub 2023 Sep 5.

ABSTRACT

OBJECTIVES: Prior research suggests that errors occur frequently for patients with medical complexity during the hospital-to-home transition. Less is known about effective postdischarge communication strategies for this population. We aimed to assess rates of 30-day (1) postdischarge incidents and (2) readmissions and emergency department (ED) visits before and after implementing a hospital-to-home intervention.

METHODS: We conducted a prospective intervention study of children with medical complexity discharged at a children’s hospital from April 2018 to March 2020. A multistakeholder team developed a bundled intervention incorporating the I-PASS handoff framework including a postdischarge telephone call, restructured discharge summary, and handoff communication to outpatient providers. The primary outcome measure was rate of postdischarge incidents collected via electronic medical record review and family surveys. Secondary outcomes were 30-day readmissions and ED visits.

RESULTS: There were 199 total incidents and the most common were medication related (60%), equipment issues (15%), and delays in scheduling/provision of services (11%). The I-PASS intervention was associated with a 36.4% decrease in the rate of incidents per discharge (1.51 versus 0.95, P = 0.003). There were fewer nonharmful errors and quality issues after intervention (1.27 versus 0.85 per discharge, P = 0.02). The 30-day ED visit rate was significantly lower after intervention (12.6% versus 3.4%, per 100 discharges, P = 0.05). Thirty-day readmissions were 15.8% versus 10.2% postintervention (P = 0.32).

CONCLUSIONS: A postdischarge communication intervention for patients with medical complexity was associated with fewer postdischarge incidents and reduced 30-day ED visits. Standardized postdischarge communication may play an important role in improving quality and safety in the transition from hospital-to-home for vulnerable populations.

PMID:37729645 | DOI:10.1097/PTS.0000000000001155